Glutathione peroxidase overexpression causes aberrant ERK activation in neonatal mouse cortex after hypoxic preconditioning.
Pediatr Res
; 72(6): 568-75, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23007029
ABSTRACT
BACKGROUND:
Preconditioning of neonatal mice with nonlethal hypoxia (HPC) protects the brain from hypoxic-ischemic (HI) injury. Overexpression of human glutathione peroxidase 1 (GPx1), which normally protects the developing murine brain from HI injury, reverses HPC protection, suggesting that a certain threshold of hydrogen peroxide concentration is required for activation of HPC signaling.METHODS:
Activation (phosphorylation) of extracellular-regulated kinase (ERK) 1/2 and Akt, and induction of hypoxia-inducible factor (HIF)-1α were assessed in the cortex, one of the main structures affected by HI and protected by HPC, at different time points after reoxygenation in wild-type (WT) and GPx1-overexpressing animals.RESULTS:
GPx1 overexpression prevented both the global and nuclear increase in activated ERK at 0.5 h after HPC and caused a significant decrease in phospho-ERK (pERK)/ERK levels at 24 h after HPC. In contrast, HIF-1α induction at the end of hypoxia was unaffected by GPx1 overexpression. In the cortex of preconditioned WT animals, enhanced pERK staining was primarily observed in neurons and to a lower extent in astrocytes and endothelial cells, with a nuclear prominence.CONCLUSION:
Aberrant activation of ERK probably explains the paradoxical reversal of HPC protection by GPx1 overexpression. The results identify hydrogen peroxide as an important mediator of neuroprotective ERK signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MAP Quinases Reguladas por Sinal Extracelular
/
Glutationa Peroxidase
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article